Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia.
Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia.
复制标题
急性心肌缺血期间的力松弛和细丝蛋白磷酸化。
DOI：
10.1002/cm.20491
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Ogut,Ozgur
中科院分区：
文献类型：
--
作者：
Han,YoungSoo;Ogut,Ozgur
缺血损害心肌功能，并可能导致心力衰竭的进展。在这项研究中，急性缺血大鼠表现出Ca 2+激活力降低以及肌球蛋白结合蛋白C、肌联蛋白和肌钙蛋白I（TnI）的Ser 23/24磷酸化减少。所有这三种蛋白质都已被证明是β-肾上腺素能受体激活（β-AR）的下游靶点，这导致了缺血期间β-AR信号转导减少导致蛋白质磷酸化减少和力松弛速率常数降低的假设。为了验证这一假设，在笼状螯合剂重氮-2光解后，从透化灌注和缺血大鼠心脏纤维记录力弛豫瞬态。弛豫瞬态最适合双指数函数，其中大部分（>70%）的力下降由快速率常数描述，该速率常数比慢速率常数快2.5倍。然而，灌注和缺血纤维之间的松弛速率常数没有不同，尽管在缺血纤维肌节蛋白磷酸化显着下降。用cAMP类似物处理灌注纤维增加了TnI的Ser 23/24磷酸化，但松弛速率常数保持不变。有趣的是，缺血性纤维的类似治疗并不影响TnI磷酸化或力松弛瞬变。因此，急性缺血不影响透化纤维的松弛速率常数。这些结果还表明，肌节蛋白磷酸化的生理水平是不可能的主要驱动力的松弛动力学透化心肌纤维。© 2010 Wiley利斯公司
Ischemia impairs myocardial function and may contribute to the progression of heart failure. In this study, rats subjected to acute ischemia demonstrated reduced Ca2+‐activated force as well as a decrease in myosin‐binding protein‐C, titin, and Ser23/24 phosphorylation of troponin I (TnI). All three proteins have been demonstrated to be downstream targets of β‐adrenergic receptor activation (β‐AR), leading to the hypothesis that decreased β‐AR signaling during ischemia leads to reduced protein phosphorylation and reduced rate constants of force relaxation. To test this hypothesis, force relaxation transients were recorded from permeabilized perfused and ischemic rat heart fibers following photolysis of the caged chelator diazo‐2. Relaxation transients were best fit by double exponential functions whereby the majority (>70%) of the force decline was described by the fast rate constant, which was ∼5 times faster than the slow rate constant. However, rate constants of relaxation between perfused and ischemic fibers were not different, despite significant decreases in sarcomeric protein phosphorylation in ischemic fibers. Treatment of perfused fibers with a cAMP analog increased Ser23/24 phosphorylation of TnI, yet the rate constants of relaxation remained unchanged. Interestingly, similar treatment of ischemic fibers did not impact TnI phosphorylation or force relaxation transients. Therefore, acute ischemia does not influence the rate constants of relaxation of permeabilized fibers. These results also suggest that the physiological level of sarcomeric protein phosphorylation is unlikely to be the primary driver of relaxation kinetics in permeabilized cardiac muscle fibers. © 2010 Wiley‐Liss, Inc.
影响因子：
3.4
作者：
Yamasaki, R;Berri, M;Granzier, H
通讯作者：
Granzier, H
影响因子：
20.1
作者：
Cazorla, O;Freiburg, A;Granzier, H
通讯作者：
Granzier, H
影响因子：
20.1
作者：
Opitz, CA;Leake, MC;Linke, WA
通讯作者：
Linke, WA